[Federal Register: November 9, 2000 (Volume 65, Number 218)]
[Notices]
[Page 67385-67388]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr09no00-86]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. 00D-1033]

Agency Information Collection Activities; Submission for OMB
Review; Comment Request; Draft Guidance for Industry on Information
Program on Clinical Trials for Serious or Life-Threatening Diseases:
Establishment of a Data Bank

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing that the
proposed collection of information listed below has been submitted to
the Office of Management and Budget (OMB) for review and clearance
under the Paperwork Reduction Act of 1995.

DATES: Submit written comments on the collection of information by
December 11, 2000.

ADDRESSES: Submit written comments on the collection of information to
the Office of Information and Regulatory Affairs, OMB, New Executive
Office Bldg., 725 17th St. NW., rm. 10235, Washington, DC 20503, Attn:
Wendy Taylor, Desk Officer for FDA.

FOR FURTHER INFORMATION CONTACT: JonnaLynn P. Capezzuto, Office of
Information Resources Management (HFA-250), Food and Drug
Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-4659.

SUPPLEMENTARY INFORMATION: In compliance with 44 U.S.C. 3507, FDA has
submitted the following proposed collection of information to OMB for
review and clearance.

Draft Guidance for Industry on Information Program on Clinical
Trials for Serious or Life-Threatening Diseases: Establishment of a
Data Bank

In the Federal Register of March 29, 2000 (65 FR 16620), FDA issued
a draft guidance to industry on

[[Page 67386]]

recommendations for investigational new drug application (IND) sponsors
on submitting information about clinical trials for serious or life-
threatening diseases to a Clinical Trials Data Bank developed by the
National Library of Medicine, National Institutes of Health (NIH). This
information is especially important for patients and their families
seeking opportunities to participate in clinical trials of new drug
treatments for serious or life-threatening diseases. The draft guidance
describes three collections of information: Mandatory submissions,
voluntary submissions, and certifications.

I. Mandatory Submissions

Section 113 of the Food and Drug Administration Modernization Act
(the Modernization Act) (Public Law 105-115) requires that sponsors
shall submit information to the Clinical Trials Data Bank when the
clinical trial: (1) Involves a treatment for a serious or life-
threatening disease, and (2) is intended to assess the effectiveness of
the treatment. The draft guidance discusses how sponsors can fulfill
the requirements of section 113 of the Modernization Act. Specifically,
sponsors should provide: (1) Information about clinical trials, both
federally and privately funded, of experimental treatments (drugs,
including biological products) for patients with serious or life-
threatening diseases; (2) a description of the purpose of the
experimental drug; (3) patient eligibility criteria; (4) the location
of clinical trial sites; and (5) a point of contact for patients
wanting to enroll in the trial.

II. Voluntary Submissions

Section 113 of the Modernization Act also specifies that sponsors
may voluntarily submit information pertaining to results of clinical
trials, including information on potential toxicities or adverse
effects associated with the use or administration of the
investigational treatment. Sponsors may also voluntarily submit studies
that are not trials to test effectiveness, or not for serious or life-
threatening diseases, to the Clinical Trials Data Bank. This notice of
proposed collection only applies to the voluntary submission of
information pertaining to studies that are not trials to test
effectiveness or not for serious or life-threatening diseases. Any
paperwork burden associated with the voluntary submission of
information pertaining to the results of clinical trials will be
discussed in the implementation document.

III. Certifications

Section 113 of the Modernization Act specifies that the data bank
will not include information relating to a trial if the sponsor
certifies to the Secretary of Health and Human Services (the Secretary)
that disclosure of the information would substantially interfere with
the timely enrollment of subjects in the investigation, unless the
Secretary makes a determination to the contrary.
Description of Respondents: A sponsor of a drug or biologic product
regulated by the agency under the Federal Food, Drug, and Cosmetic Act
or section 351 of the Public Health Service Act (42 U.S.C. 262) who
submits a clinical trial to test effectiveness of a drug or biologic
product for a serious or life-threatening disease.
Burden Estimate: The information required under section 113(a) of
the Modernization Act is currently submitted to FDA under 21 CFR part
312, and this collection of information is approved under OMB Control
Number 0910-0014 until September 30, 2002, and, therefore, does not
represent a new information collection requirement. Instead,
preparation of submissions under section 113 of the Modernization Act
involves extracting and reformatting information already submitted to
FDA. Although the procedures (where and how) for the actual submission
of this information have not yet been developed, the agency believes it
has an adequate basis for the determination of the hourly burden
related to extracting and reformatting this information. The chart
below provides an estimate of the annual reporting burden for the
submission of information to satisfy requirements of section 113 of the
Modernization Act. The Center for Drug Evaluation and Research (CDER)
is currently receiving 99.2 new protocols per week (mean value, March
through May 1999), or 5,158 new protocols per year. CDER anticipates
that protocol submission rates will remain at or near this level in the
near future. Of these new protocols, an estimated two-thirds are for
serious or life-threatening diseases and would be subject to either
voluntary or mandatory reporting requirements under section 113 of the
Modernization Act. Two-thirds of 5,158 protocols per year is 3,439 new
protocols per year. An estimated 65 percent of the new protocols for
serious or life-threatening diseases submitted to CDER are for clinical
trials involving assessment for effectiveness, and are subject to the
mandatory reporting requirements under section 113 of the Modernization
Act. Sixty-five percent of 3,439 protocols per year is 2,235 new
protocols per year subject to mandatory reporting. The remaining 2,923
new protocols per year are subject to voluntary reporting.
The Center for Biologics Evaluation and Research (CBER) is
currently receiving 29 new protocols per month, or 348 new protocols
per year. CBER anticipates that protocol submission rates will remain
at or near this level in the near future. An estimated two-thirds of
the new protocols submitted to CBER are for clinical trials involving a
serious or life-threatening disease, and would be subject to either
voluntary or mandatory reporting requirements under section 113 of the
Modernization Act. Two-thirds of 348 new protocols per year is 232 new
protocols per year. An estimated 65 percent of the new protocols for
serious or life-threatening diseases submitted to CBER are for clinical
trials involving assessments for effectiveness. Sixty-five percent of
232 protocols per year is an estimated 151 new protocols per year
subject to the mandatory reporting requirements under section 113 of
the Modernization Act. The remaining 197 new protocols per year are
subject to voluntary reporting.
The estimated total number of new protocols for serious or life-
threatening diseases subject to mandatory reporting requirements under
section 113 of the Modernization Act is 2,235 for CDER plus 151 for
CBER, or 2,386 new protocols per year. The remainder of protocols
submitted to CDER or CBER will be subject to voluntary reporting,
including clinical trials not involving a serious or life-threatening
disease as well as trials in a serious or life-threatening disease but
not involving assessment of effectiveness. Therefore, the total number
of protocols (5,506) minus the protocols subject to mandatory reporting
requirements (2,386) will be subject to voluntary reporting, or 3,120
protocols.
It was originally estimated that the protocol submissions to the
data bank will be updated 2.5 times per year under section 113 of the
Modernization Act. In the Federal Register of March 29, 2000, the
agency requested comments on the proposed collection of information.
One comment was received. The comments stated that FDA greatly
underestimated the burden by excluding multicenter studies and not
accounting for the quality control review of the data before it is
submitted to the data bank. We estimated that 5,506 new protocols are
submitted each year and each new protocol is updated 2.5 times per year
with information that would necessitate

[[Page 67387]]

a change in the data bank. We further estimated that each change
requires an average of 5.6 hours resulting in 77,084 hours spent by
respondents per year. These estimates included protocols subject to
mandatory and voluntary reporting requirements.
For the revised justification, we reviewed actual IND data from
1997 to 1999, and as a result of our reanalysis we incorporated new
estimates that consider multicenter studies. The average number of IND
amendments submitted annually for protocol changes (e.g., changes in
eligibility criteria) was 4,019 for CDER and 1,441 for CBER. The
average number of IND amendments submitted annually for new
investigators was 7,745 for CDER and 1,349 for CBER. The number of
protocol changes and new investigators was apportioned proportionally
between mandatory and voluntary submissions. We recognize that single
submissions may include information about multiple sites.
Generally, there is no submission to FDA when an individual study
site is no longer recruiting study subjects. For this analysis, we
assumed that the number of study sites closed each year is similar to
the number of new investigator amendments received by FDA (7,745 CDER
and 1,349 CBER).
Generally, there is no submission to FDA when the study is closed
to enrollment. We estimate the number of protocols closed to enrollment
each year is similar to the number of new protocols submitted (5,158
CDER and 348 CBER).
The hours per response is the estimated number of hours that a
respondent would spend preparing the information to be submitted under
section 113(a) of the Modernization Act, including the time it takes to
extract and reformat the information. FDA has been advised that some
sponsors lack information system capabilities enabling efficient
collection of company-wide information on clinical trials subject to
reporting requirements under section 113(a) of the Modernization Act.
The estimation of burden under section 113(a) reflects the relative
inefficiency of this process for these firms.
Based on its experience reviewing IND's, and consideration of the
above information, FDA estimated that approximately 5.6 hours on
average would be needed per response (mean value), based on an
estimated 3.2 hours for data extraction and 2.4 hours for reformatting.
We considered quality control issues when developing the original
burden estimates of 3.2 hours for data extraction and the 2.4 hours
estimated for reformatting. Additionally, the data entry system being
developed incorporates features that will further decrease the
sponsor's time requirements for quality control procedures. No new
estimates for quality control are included in the reanalysis.
The new estimate continues to use an average of 5.6 hours per
response for calculations related to new submissions. Changes related
to the addition and deletion of investigational sites will involve
minimal resource commitments from the sponsor. Further, many protocol
changes will not require changes to the data bank. Other protocol
changes will require minimal time to make changes to the data bank
(e.g., modification of eligibility criteria). The 5.6 hours per
response estimate for these types of responses is high.
A sponsor of a study subject to the requirements of section 113 of
the Modernization Act will have the option of submitting data under
that section or certifying to the Secretary that disclosure of
information for a specific protocol would substantially interfere with
the timely enrollment of subjects in the clinical investigation. FDA
has no means to accurately predict the proportion of protocols subject
to the requirements of section 113 of the Modernization Act that will
be subject to a certification submission. However, it is anticipated
that the burden associated with such certification will be comparable
to that associated with submission of data regarding a protocol.
Therefore, the overall burden is anticipated to be the same, regardless
of whether the sponsor chooses data submission or certification for
nonsubmission. The table below reflects the estimate of this total
burden.
FDA estimates the burden of this collection of information as
follows:

Table 1.--Estimated Annual Reporting Burden ¹
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New Recruitment Protocol New Sites Total Hours per
Protocols Complete Changes Investigators Closed Responses Response Total Hours
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CDER (mandatory).............................. 2,235 2,235 1,728 3,330 3,330 12,858 5.6 72,005
CBER (mandatory).............................. 151 151 620 580 580 2,082 5.6 11,659
CDER (voluntary).............................. 2,923 2,923 2,291 4,415 4,415 16,967 5.6 95,015
CBER (voluntary).............................. 197 197 821 769 769 2,753 5.6 15,417
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Total......................................... 194,096
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\1\ There are no capital and startup, or operation and maintenance costs associated with this collection of information.

The revised burden estimate for responses (34,660) is 2.5 times the
original estimate (13,765).
We believe that the original burden estimate of 77,084 hours spent
per year underestimated the burden. The new estimate, 194,096 hours per
year (34,660 responses x 5.6 hours per response), more accurately
reflects the burden.
NIH and FDA are considering a pilot program for the electronic
submission of protocol information over the Internet. The purpose of
the pilot project is twofold. First, the pilot project will allow FDA
to test its systems for receiving electronic submissions under section
113 of the Modernization Act. Second, the pilot project will provide
opportunities for volunteers to gain experience in using the prototype
system that will enable them to provide technical feedback on how well
the system is working, and also to offer suggestions for change. The
experience gained from this pilot project also will facilitate the
development of the implementation plan.
FDA anticipates that up to 25 sponsors will volunteer to
participate in a pilot program involving the electronic submission of
protocol information over the Internet. Protocol information entered
into the system during the pilot project will be included in the
Clinical Trials Data Bank (ClinicalTrials.gov). We estimate that each
sponsor will include 10 protocols in the data bank. We estimate that
each protocol will be modified two times and add three new sites. It is
assumed that the sites will remain open for the duration of the pilot.
The one-time burden estimate for the pilot program is 8,400 (1,500
responses x 5.6 hours/response). Since

[[Page 67388]]

the pilot protocols will be included in the ClinicalTrials.gov data
bank, the estimated annual burden for the first year will be reduced by
the number of protocols included in the pilot.
FDA estimates the burden of the collection of information as
follows:

Table 2.--Estimated Annual Reporting Burden ¹
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Protocol New Total Annual Hours per
New Protocols Changes Investigators Responses Response Total Hours
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CDER 200 400 600 1,200 5.6 6,720
CBER 50 100 150 300 5.6 1,680
Total 8,400
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\1\ There are no capital and startup, or operation and maintenance costs associated with this collection of
information.

Dated: November 6, 2000.
Margaret M. Dotzel,
Associate Commissioner for Policy.
[FR Doc. 00-28851 Filed 11-8-00; 8:45 am]
BILLING CODE 4160-01-F /